The following processes are known for preparing a quinazolin-4-one compound from an anthranilic acid compound.
EP 1029853 discloses a process for preparing 6-iodoquinazolin-4-one by reacting 5-iodoanthranilic acid with formamidine acetate in ethanol for 20 hours. This process has problems in that the reaction period is long, and it is necessary to use expensive formamidine in an excessive amount.
Chem. Pharm. Bull., 46, 1926 (1998) describes a process for preparing the quinazolin-4-one by reacting anthranilic acid with formamide. This process has a problem in that teratogenetic formamide is used in an excessive amount.
J. Org. Chem., 18, 138 (1953) describes a process for preparing the quinazolin-4-one by reacting methyl anthranilate and formamide in the presence of an ammonium formate. This process has problems in that teratogenetic formamide is reacted at an elevated temperature in an excessive amount and the yield of the desired compound is low.
Any of the above-described processes have problems, and hence they are not favorable as industrially applicable processes.
WO 01/21594 describes a process for a 6-alkoxy-7-aminoalkoxyquinazolin-4-one compound or a 7-alkoxy-6-aminoalkoxyquinazolin-4-one compound. For instance, ethyl 3-methoxy-4-(3-morpholinopropoxy)-6-aminobenzoate is reacted with formamide to give 6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-one in 68% yield. This process, however, has a problem as an industrially applicable process in that the yield is low, and the teratogenetic formamide is reacted at an elevated temperature in an excessive amount.
JP-A-2001-519788 describes a process for preparing a 5-alkoxy-4-halogenoalkoxyanthranilic acid compound from a 5-alkoxy-4-halogenoalkoxy-2-nitrobenzoic acid compound. For example, methyl 4-(3-chloropropoxy)-5-methoxy-2-nitrobenzoate is reacted with a very excessive amount of iron and ammonium chloride in a mixture of water and methanol, to give methyl 2-amino-4-(3-chloropropoxy)-5-methoxybenzoate (i.e., ethyl 4-(3-chloropropoxy)-5-methoxyanthranilate) in 90% yield.
J. Med. Chem., 44, 3965 (2001) describes a process for preparing a 4-alkoxy-5-halogenoalkoxyanthranilic acid compound from a 4-alkoxy-5-halogenoalkoxy-2-nitrobenzoic acid compound. For example, methyl 5-(3-chloropropoxy)-4-methoxy-2-nitrobenzoate is reacted with a very excessive amount of iron and ammonium chloride in a mixture of water and methanol, to give methyl 2-amino-5-(3-chloropropoxy)-4-methoxybenzoate (i.e., methyl 5-(3-chloropropoxy)-4-methoxyanthranilate) in 93% yield.
These processes, however, have problems as industrially applicable processes in that a very excessive amount of iron is used and a complicated post-treatment process is required.
WO 02/36587 describes a process for preparing a 5-alkoxy-4-halogenoalkoxy-2-nitrobenzoic acid compound from a 3-alkoxy-4-hydroxybenzoic acid compound. For example, ethyl vanillate (i.e., ethyl 4-hydroxy-3-methoxybenzoate) is reacted with 3-bromo-1-chloropropane in an aqueous potassium carbonate solution in the presence of N-butyl-ammonium bromide to produce ethyl 4-(3-chloropropoxy)-3-methoxybenzoate, and the ethyl 4-(3-chloropropoxy)-3-methoxybenzoate is reacted with 70% nitric acid in a mixture of dichloromethane and acetic acid, to give ethyl 4-chloropropoxy-3-methoxy-2-nitrobenzoate in 82% yield (based on the amount of ethyl vanillate).
The aforementioned J. Med. Chem., 44, 3965 (2001) further describes a process for preparing a 4-alkoxy-5-halogenoalkoxy-2-nitrobenzoic acid compound from a 4-alkoxy-3-hydroxybenzoic acid compound. For example, methyl 3-hydroxy-4-methoxybenzoate is reacted with 3-chloropropyl p-toluenesulfonate in an aqueous potassium carbonate solution in the presence of tricaprylmethyl ammonium chloride to produce methyl 3-(3-chloropropoxy)-4-methoxybenzoate, and the methyl 3-(3-chloropropoxy)-4-methoxybenzoate is reacted with 70% nitric acid in a mixture of dichloromethane and acetic acid, to give methyl 5-(3-chloropropoxy)-4-methoxy-2-nitrobenzoate in 61% yield (based on the amount of methyl 3-hydroxy-4-methoxybenzoate).
The above-mentioned process, however, has problems as an industrially applicable process in that the reaction utilizes a complicated two phase reactions, the reaction procedure is complicated, an industrially unfavorable dichloromethane solvent is necessarily employed, the reaction period is long, and the yield is low.